Women with the highest bone mass are at a much greater risk of postmenopausal breast cancer than those with lower bone mass, according to the results of a long-term epidemiological study supported by the National Institutes of Health (NIH). The study's results are published in the February 27, 1997, issue of the New England Journal of Medicine.

"This report confirms a strong association between high bone mass and increased risk of breast cancer and indicates a need for further studies to examine these risks and determine intervention where appropriate," said Dr. Claude Lenfant, director of the National Heart, Lung, and Blood Institute (NHLBI) at the NIH.

Although investigators have identified a connection between estrogen and the development of breast cancer, it has been difficult to adequately measure estrogen exposure over time. "Bone mass may be a way of summarizing the body's cumulative exposure to estrogen, and therefore, might represent a potent tool for predicting who is at greatest risk of breast cancer," said Dr. Douglas Kiel, a co-author of the study and Associate Director of Medical Research at the Hebrew Rehabilitation Center for the Aged.

The study examined 1,373 women who received hand x-rays between 1967 and 1970 as part of the NHLBI's Framingham Heart Study, an ongoing epidemiological study in Framingham, Massachusetts. Using the x-rays, the researchers calculated the thickness of a bone in each woman's hand to determine its density. These women were then monitored over a 26-year period, during which time 91 women developed postmenopausal breast cancer. After adjusting for multiple breast cancer risk factors, researchers determined that women in the highest bone mass group had 3.5 times the risk of getting breast cancer compared to those in the lowest quartile of bone mass.

A variety of factors contribute to both maximizing bone mass and influencing breast development and the risk of breast cancer, according to Dr. Joan McGowan, director of the Musculoskeletal Diseases Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. "We need to clarify if estrogen is the link between bone mass and breast cancer, and if it is, whether it is lifetime exposure or effects that occur at a critical period, such as adolescence," said Dr. McGowan.

Although this study did not investigate the direct connection between estrogen levels or hormone replacement therapy (HRT) and breast cancer risk, it adds to the increasing evidence about the effects of estrogen, said Dr. Lenfant. However, he also cautioned that the findings should be kept in perspective since, for most women, estrogen may provide crucial benefits against heart disease and osteoporosis.

Heart disease is the leading cause of death among American women. While about 44,000 women died of breast cancer in 1994, approximately 370,000 died of heart disease.

The Postmenopausal Estrogen/Progestin Interventions Trial (PEPI), an NHLBI-administered study, found that HRT helps improve some heart disease risk factors. For instance, it causes significant increases in HDL or "good" cholesterol and decreases in LDL or "bad" cholesterol.

The PEPI study also found that HRT increases bone density, helping to reduce the risk of osteoporosis, a severe thinning of the bones that can lead to an increased risk of bone fractures and serious complications including pain, loss of mobility, and death. About 25 million people in the U.S. have or are at risk of developing osteoporosis.

"Additional research is needed to pinpoint the modifiable risks associated with cancer, heart disease, and osteoporosis, and how they interrelate. For example, the NIH Women's Health Initiative is currently conducting a large, randomized clinical trial to determine the direct benefits and risks of HRT on postmenopausal women," said Dr. Lenfant.

For postmenopausal women who need to make treatment decisions now, before ongoing study results are available, Dr. Lenfant advised women to consult their physicians and weigh their individual health risks before deciding on the best course of action.

The study was conducted by lead author Dr. Yuqing Zhang and other researchers and supported by the National Heart, Lung, and Blood Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute, components of the NIH.

Dr. Douglas Kiel is available for comment at (617) 325-8000 x384. Dr. Joan McGowan is also available for comment and can be reached through the NIAMS Communications Office at (301) 496-8190. In addition, Dr. David Felson, co-author of the study, may be reached through the Boston University School of Medicine Communications Office at (617) 638-8491. For background information on the Framingham Heart Study and to interview Dr. Daniel Levy, director of Framingham, contact the NHLBI Communications Office at (301) 496-4236.

NHLBI press releases, fact sheets, and other materials are available online at the following website: http://www.nhlbi.nih/nhlbi/nhlbi.htm.